Search Results (21,655)

Background: Among the 15 human (h) carbonic anhydrase (CA; EC 4.2.1.1) isoforms, hCA IX and XII are particularly important due to their roles in tumor cell growth and survival, identifying them as promising targets for anticancer therapy. As a result, considerable effort has been directed toward the development of novel inhibitors that are highly selective for these isoforms. Methods: A library of twelve novel N-aryl-2-(4-sulfamoylphenyl)hydrazine-1-carbothioamides 3 along with two new N-aryl-2-(4-sulfamoylphenyl)hydrazine-1-carboxamide derivatives 5 were synthesized and their inhibition abilities were tested against four human carbonic anhydrase isozymes (hCA I, II, IX and XII) related to some global diseases including glaucoma, cancer and osteoporosis. Results: All compounds exhibited potent inhibition of the tested isoforms in the nanomolar range. Compound 3i showed the highest inhibition of hCA I activity but demonstrated poor selectivity toward the other isoforms. Compound 3h displayed superior selectivity for hCA II over hCA I (hCA I/II = 37) and exhibited 2.5-fold higher inhibitory activity compared to acetazolamide (AAZ). Among the tested compounds, 3l (K_i = 32.1 nM) demonstrated markedly improved selectivity for hCA IX over hCA I, II, and XII relative to the standard drug. Notably, compound 3a showed the most potent inhibition against hCA XII (K_i = 6.8 nM), comparable to AAZ, while exhibiting significantly greater selectivity over off-target isoforms and the other tumor-associated isozyme (hCA IX/XII = 20 versus hCA IX/XII = 4.5 for AAZ). Conclusions: The present study suggests potent lead compounds as selective hCA IX and XII inhibitors with anticancer activity. Full article

Grape stems are undervalued winemaking by-products that constitute a promising source of bioactive phenolics with notable antioxidant potential and diverse industrial applications, including food preservation, cosmetics, and pharmaceuticals. Effective valorisation of this resource requires not only efficient extraction strategies, but also the strategic selection of grape stem varieties to tailor phenolic profiles for specific high-value uses. In this study, a comparative assessment of three extraction techniques, pressurized liquid extraction (PLE), ultrasound-assisted extraction (UAE), and conventional solid–liquid extraction (SLE), across six grape stem varieties was conducted. By integrating spectrophotometric analyses of total phenolics and antioxidant capacity with HPLC-DAD profiling of individual phenolic compounds, the combined influence of extraction method and varietal composition on phenolic recovery was demonstrated. PLE and UAE significantly enhanced both yield and antioxidant capacity relative to SLE, with PLE providing the broadest spectrum of phenolic compounds. Varietal differences were also pronounced; e.g., Cabernet Sauvignon stems yielded higher antioxidant phenolic compound content, particularly under UAE, reinforcing the importance of aligning extraction technique and stem variety with the intended functional application. Full article

Climate change has exacerbated flood risks for urban infrastructure, rendering sewage treatment facilities (STFs) particularly vulnerable due to their typical low-lying topographic placement. However, conventional flood risk assessment methodologies often rely solely on physical hazard parameters such as inundation depth, neglecting the functional interdependencies and operational criticality of individual treatment units. To address this limitation, this study proposes the Integrated Hydro-Operational Risk Assessment (IHORA) framework. The IHORA framework synthesizes 2D hydrodynamic modeling with a modified Hazard and Operability Study(HAZOP) study to systematically identify unit-specific physical failure thresholds and employs the Analytic Hierarchy Process (AHP) to quantify the relative operational importance of each process based on expert elicitation. The framework was applied to an underground STF under both fluvial flooding and internal structural breach scenarios. The results revealed a significant risk misalignment in traditional assessments; vital assets like electrical facilities were identified as high-risk hotspots despite moderate physical exposure, due to their high operational weight. Furthermore, Cause–Consequence Analysis (CCA) was utilized to trace cascading failure modes, bridging the gap between static risk metrics and dynamic emergency response protocols. This study demonstrates that the IHORA framework provides a robust scientific basis for prioritizing mitigation resources and enhancing the operational resilience of environmental facilities. Full article

Background/Objectives: Osteoporosis is a major global health concern, and early risk assessment plays a crucial role in fracture prevention. Although demographic, clinical, and lifestyle factors are commonly incorporated into screening tools, their relative importance within data-driven prediction frameworks can vary substantially across datasets. Rather than aiming to identify novel predictors, this study evaluates the stability and behavior of established osteoporosis risk factors using statistical inference and machine learning-based feature selection methods across heterogeneous data sources. We further examine whether simplified and near-minimal models can achieve predictive performances comparable to that of full-feature configurations. Methods: An open-access Kaggle dataset (n = 1958) and a retrospective clinical dataset from the University of Phayao Hospital (n = 176) were analyzed. Feature relevance was assessed using logistic regression, likelihood ratio testing, MRMR, ReliefF, and unified importance scoring. Multiple predictor configurations, ranging from full-feature to minimal and near-minimal models, were evaluated using decision tree, support vector machine, k-nearest neighbor, naïve Bayes, and efficient linear classifiers. External validation was performed using hospital-based records. Results: Across all analyses, age consistently emerged as the dominant predictor, followed by corticosteroid use, while other variables showed limited incremental predictive contributions. Simplified models based on age alone or age combined with medication-related variables achieved performances comparable to full-feature models (accuracy ≈91% and AUC ≈ 0.95). In addition, near-minimal models incorporating gender alongside age and medications demonstrated a favorable balance between discrimination and computational efficiency under external validation. Although overall performance declined under distributional shift, naïve Bayes and efficient linear classifiers showed the most stable external behavior (AUC = 0.728–0.787). Conclusions: These findings indicate that stability-driven feature selection primarily reproduces well-established epidemiological risk patterns rather than identifying novel predictors. Minimal and near-minimal models—including those incorporating gender—retain acceptable performances under external validation and are methodologically efficient. Given the limited size and single-center nature of the external cohort, the results should be interpreted as preliminary methodological evidence rather than definitive support for clinical screening deployment. Further multi-center studies are required to assess generalizability and clinical relevance. Full article

In the wave theory of saturated soils, pore tortuosity is an important physical property for quantifying the added mass force caused by the relative acceleration between solid and liquid phases. However, this inertial force is often ignored for simplicity in practical applications. To investigate the influence of pore tortuosity on the propagation of compressional waves in saturated soils, a system of generalized governing equations for one-dimensional infinitesimal strain elastic waves is solved using the Laplace transform method. Semi-analytical solutions are obtained for the spatiotemporal distributions of the excess pore water pressure, the pore water velocity, and the soil particle velocity caused by a step load perturbation under undrained conditions. These solutions are used to evaluate the effects of pore tortuosity on the velocities and amplitudes of fast and slow compressional waves. The results show that pore tortuosity has an insignificant effect on the propagation of fast compressional waves, but for slow compressional waves, the larger the pore tortuosity is, the lower the wave velocity and the larger the wave amplitude. Ignoring the influence of pore tortuosity can lead to an underestimation of the arrival time of slow compressional wave. The propagation of this wave is limited to a distance of approximately 1 m away from the loading boundary. This research finding is purely theoretical. For further experimental validation, it is suggested to detect the slow compressional wave by placing miniature acoustic receiving transducers as close as possible to the loading or transmitting surface. The proposed solutions are also useful for calibrating sophisticated numerical codes for dynamic consolidation of saturated soils and wave transmission in porous media. Full article

Mitral valve orifice area is a key functional metric that depends on complex geometric features, motivating a systematic assessment of the relative influence of these parameters. In this study, the mitral valve geometry is parameterized using twelve geometric variables, and a global sensitivity analysis based on Sobol indices is performed to quantify their relative importance. Because global sensitivity analysis requires many simulations, a Gaussian Process regressor is developed to efficiently predict the orifice area from the geometric inputs. Structural simulations of the mitral valve are carried out in Abaqus, focusing exclusively on the valve mechanics. The predicted distribution of orifice areas obtained from the Gaussian Process shows strong agreement with the ground-truth simulation results, and similar agreement is observed when only the most influential geometric parameters are varied. The analysis identifies a subset of geometric parameters that dominantly govern the mitral valve orifice area and can be reliably extracted from medical imaging modalities such as echocardiography. These findings establish a direct link between echocardiographic measurements and physics-based simulations and provide a framework for patient-specific assessment of mitral valve mechanics, with potential applications in guiding interventional strategies such as MitraClip placement. Full article

The transition to renewable energy is generating numerous changes across different continents, some with greater impact than others, but the progress achieved is recognized and widely accepted. In particular, there are various solutions that include electric vehicles as elements that influence grid behavior when connected. Higher levels of electric vehicle penetration can present opportunities and solutions related to energy storage, V2G connections encompassing the distribution system, and long-term evaluation. High participation in V2G connections maintains the availability of the electrical system, while the high proportion of variable renewable energy sources forms the backbone of the overall electrical system. This study presents a systematic review of V2G systems in the Americas. The design of the Sustainable Mobility scenario and the high participation of V2G maintain the balance of the electrical system for most of the day, simplifying storage equipment requirements. Consequently, the influence of V2G systems on energy storage is an important outcome that must be considered in the energy transition and presents development opportunities for the various countries that make up the Americas. The stored electricity will not only serve as storage for future grid use, but V2G batteries will also act as a buffer between generation from diversified renewable sources and the end-use stage. This article shows that research on the design of V2G energy systems in scientific publications is relatively recent, but it has gained increasing attention in recent years. In total, 151 articles published since 1995 have been identified and analyzed. The overall result indicates that North American countries have developed the most V2G applications, and their deployment in the coming years will be significant. Meanwhile, in South and Central America, these systems are not yet being fully utilized due to the lack of growth in the electric vehicle market. Full article

Background: Advanced endometrial cancer is associated with poor survival. With the advent of molecular classification and novel systemic therapies—including immunotherapy and targeted agents—treatment regimens have become increasingly complex. While these approaches aim to improve survival, they also potentially introduce long-term toxicities and treatment burden, reinforcing the importance of incorporating health-related quality of life (HRQoL) and patient-reported outcomes (PROs) into clinical trials. Methods: A systematic review was conducted of phase III randomized controlled trials (RCTs) in advanced, recurrent, or metastatic endometrial cancer evaluating systemic treatment registered on ClinicalTrials.gov and published up to 30 November 2025. Extracted data included study characteristics, HRQoL instruments, reporting formats, adherence to CONSORT-PRO, and timing of HRQoL dissemination (relative to primary efficacy reports). Results: Eight phase III RCTs published between 2020 and 2024 were included. Although HRQoL was consistently designated as a secondary endpoint, reporting within pivotal efficacy publications was limited. Most reports presented mean changes from baseline using the EORTC QLQ-C30, QLQ-EN24, and EQ-5D-5L. None of the primary reports reported time-to-deterioration analyses or the proportions of patients improving/deteriorating. Adherence to CONSORT-PRO was low, with only a minority of items addressed. Dedicated QoL publications were delayed by up to 25 months after primary efficacy reports and typically appeared in journals with lower impact factors. Conclusions: Despite routine inclusion of HRQoL measures in trial protocols, reporting remains inconsistent, limited in scope, and often delayed. Strengthening adherence to established frameworks is essential to ensure that HRQoL endpoints are predefined, analytically robust, and disseminated alongside efficacy data—particularly in a rapidly evolving therapeutic landscape. Full article

This study investigated the impact of post-activation performance enhancement (PAPE) on the parameters of the 3 min all-out test (3MT) in non-motorized tethered running, applying the concept of complex networks for integrative analysis. Ten recreational runners underwent anthropometric assessments, a one-repetition maximum test (1RM), a running ramp test, and 3MT trials under both PAPE and CONTROL conditions across five separate sessions. The conditioning activity consisted of two sets of six back squats at 60% 1RM. For each scenario, complex network graphs were constructed and analyzed using Degree, Eigenvector, PageRank, and Betweenness centrality metrics. In the PAPE condition, anthropometric parameters and parameters related to aerobic efficiency exhibited greater centrality, ranking among the top five nodes. Paired Student’s t-tests (p ≤ 0.05) revealed significant differences between conditions for end power (EP-W) (CONTROL: 407.83 ± 119.30 vs. PAPE: 539.33 ± 177.10 (effect size d = −0.84)) and end power relativized by body mass (rEP-W·kg⁻¹) (CONTROL: 5.38 ± 1.70 vs. PAPE: 6.91 ± 2.00 (effect size d = −0.76)), as well as for the absolute and relative values of peak output power, mean output power, peak force, and mean force. These findings suggest that PAPE alters the configuration of complex networks, increasing network density, and may enhance neuromuscular function and running economy. Moreover, PAPE appears to modulate both aerobic and anaerobic contributions to performance. These results highlight the importance of network-based approaches for advancing exercise science and providing individualized strategies for training and performance optimization. Full article

Changes in preservation conditions act as an important environmental filter driving shifts in microbial communities. However, the precise identities, functional traits, and ecological mechanisms of the dominant agents driving stage-specific deterioration remain insufficiently characterized. This study investigated microbial communities and dominant fungal degraders in waterlogged versus dried bamboo slips using amplicon sequencing, multivariate statistics, and microbial isolation. Results revealed compositionally distinct communities, with dried slips sharing only a small proportion of operational taxonomic units (OTUs) with waterlogged slips, while indicating the persistence of a subset of taxa across preservation states. A key discovery was the dominance of Fonsecaea minima (92% relative abundance) at the water-solid-air interface of partially submerged slips. Scanning electron microscopy (SEM) and pyrolysis-gas chromatography/mass spectrometry (Py-GC/MS) indicate that this fungus forms melanin-rich, biofilm-like surface structures, suggesting enhanced surface colonization and stress resistance. In contrast, the fungal community isolated from dried slips was characterized by Apiospora saccharicola associated with detectable xylanase activity. Meanwhile, the xerophilic species Xerogeomyces pulvereus dominated (99% relative abundance) the storage box environment. Together, these results demonstrate that preservation niches select for fungi with distinct functional traits, highlighting the importance of stage-specific preservation strategies that consider functional traits rather than taxonomic identity alone. Full article

Based on ongoing experimental research, the present manuscript presents the effect of the slippage of a steel reinforcing bar due to corrosion on the chord rotation and deformation of corroded Reinforced Concrete members. The experimental results recorded that the increase in the corrosion level of the steel led to bond strength loss and relative slip between the steel and concrete, which was increased from 1.5 mm in non-corroded conditions to 3.5 mm even at low corrosion levels, up to a 5% steel mass loss. This slippage of corroded reinforcing bars from the anchorage leads to a proportional increase in terms of chord rotation due to pull out resulting in an additional increase in the displacement of the column’s top. In conclusion, the present study highlights the great importance of the contribution of the resulting slippage of a steel reinforcing bar due to corrosion in the calculation of the limit chord rotation (column–beam), a term which is of major importance in the assessment of the structural integrity of old RC structures, which was introduced as an adequacy requirement by both Eurocode 8-3 and the Greek Code of Structural Interventions (KAN.EPE). Full article

Tree canopies in urban areas have many important ecosystem functions, and councils have targets to increase urban tree canopy area, which has proved challenging. Urban centres have large areas of impervious surfaces, and there is a perception that impervious surfaces are harmful for urban tree growth as water cannot penetrate the soil in which trees are growing. We investigated tree crown growth of young trees of eight common urban tree species in a suburb of Melbourne, Australia, that either grew in streets that were impacted by impervious surfaces or in parks. Four tree species had shown sensitivity to rainfall by lower crown growth in a low-rainfall suburb before, while the other four species had similar crown growth in high- and low-rainfall suburbs. We identified 40 trees per species and location (street vs. park) that were planted between 2009 and 2011 and measured their tree crown area in 2014 and again in 2018 using remote-sensed images. Trees that grew in streets that were impacted by impervious surfaces had larger crowns in 2014 than trees in parks, but both showed similar crown growth rates of 2.3 m² yr⁻¹ in the four-year period. Only one species (Eucalyptus sideroxylon A.Cunn ex Woolls) had a statistically significant greater relative crown growth rate in parks compared to streets. There was no statistically significant difference in the relative or absolute crown growth rates in tree species that have shown a previous sensitivity to rainfall compared to those that were insensitive to rainfall. Our data indicate that impervious surfaces had no detrimental impact on tree crown growth. It is possible that trees grown in streets have sufficient water resources and may benefit from the lack of competition for water, whereas trees in parks must compete for water resources with other plants. Full article

The water yield (WY) service is a critical ecosystem service in arid regions, and understanding its spatiotemporal heterogeneity and controls is important for sustainable watershed management. Annual water yield (WY) in the Aksu River Basin (ARB), China, from 2000 to 2020 was simulated using the InVEST model, with validation against observed runoff (NSE = 0.840, R² = 0.846, RMSE = 1.787). The results revealed a decline in WY from 66.49 mm in 2000 to 43.15 mm in 2015, while retaining a clear north–south gradient, with higher values in the north. Areas showing decreasing and increasing trends accounted for 45.34% and 3.14% of the basin, respectively. WY exhibited strong spatial autocorrelation (global Moran’s I = 0.912–0.941), with high-value clusters in the north and low-value clusters in the south. GeoDetector identified precipitation, temperature, and potential evapotranspiration as key drivers (q = 0.889, 0.880, and 0.832, respectively), with precipitation-related interactions generally exceeding 0.9, indicating enhanced explanatory power through multi-factor coupling. After variable screening and collinearity control, MGWR revealed spatially varying effects of drivers and significant spatial non-stationarity. Overall, despite the declining trend, WY in the ARB maintained a relatively stable spatial structure, with its heterogeneity primarily driven by the coupling of climatic forcing and topographic constraints, providing a scientific basis for zonal water resource management in arid river basins. Full article

Background/Objectives: Significant heterogeneity in the treatment response to peroxisome proliferator-activated receptor γ (PPARγ) agonists exists, and predictive factors for their efficacy remain unclear. We aimed to assess the relationships between routinely available clinical features and the efficacy of PPARγ agonists and pan-PPAR agonists by meta-regression analysis. Methods: We searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) and included randomised controlled trials involving type 2 diabetes patients with 12-week or longer treatment durations with PPARγ agonists or pan-PPAR agonists published before 11 November 2023 (PROSPERO registration number: CRD42024578987). We conducted mixed-effect meta-regression analyses between baseline variables and treatment response. Moreover, we developed a machine learning-based meta-forest model and ranked the relative importance of each variable. Results: In 147 studies involving 29,250 participants, PPARγ and pan-PPAR agonists significantly reduced HbA1c (mean difference(MD) = −0.8876 [95% confidence interval (CI): −0.8999, −0.8754]; p < 0.0001, I² = 96.0%) and FPG = (MD = −1.7900 [95% CI: −1.9137, −1.6663]; p < 0.0001, I² = 92.0%). Multivariable association analysis suggested that a greater proportion of female participants (β = 0.0066 [95% CI: 0.0012, 0.0121]; p = 0.017), younger age (β = −0.0314 [95% CI: −0.05, −0.0129]; p = 0.0009) and lower HDL-C levels (β = −0.9304 [95% CI: −1.5176, −0.3431]; p = 0.0019) were significantly associated with a greater decrease in HbA1c. A greater proportion of female participants (β = 0.0112 [95% CI: 0.0019, 0.0205]; p = 0.0178) and lower baseline HDL-C levels (β = −1.8722 [95% CI: −2.812, −0.9323]; p < 0.0001) were significantly associated with a greater decrease in FPG. These variables also ranked among the top five most important predictors of drug response in the meta-random forest models. Conclusions: Our study demonstrated that female sex, younger age, and lower HDL-C levels were associated with greater glycaemic lowering effect from PPARγ and pan-PPAR agonists. Full article

The insect gut microbiome contributes to various host physiological processes and behaviors, such as digestion, nutrient absorption, immunity, mate choice, and fecundity. The social environment can shape gut microbial communities. Mixed-sex vs. female-only rearing is an important social context because it differs in exposure to the opposite sex and mating opportunities, which may in turn affect female physiology that may influence their gut microbiome. Despite the growing recognition of these social-microbial interactions, most studies have relied on 16S rRNA amplicon sequencing or qPCR, which provide only coarse taxonomic resolution and limited functional insight. In this study, we used whole-genome shotgun metagenomics to examine changes in microbial diversity and functional gene composition in the female field cricket Teleogryllus occipitalis (Serville) (Orthoptera: Gryllidae) reared under two social conditions: mixed-sex rearing and female-only rearing. Species richness and diversity analyses revealed that community composition separated between females from mixed-sex and female-only rearing. Functional profiling indicated higher relative abundances of genes annotated to nutrient processing and inter-bacterial competition in females from mixed-sex rearing, whereas females from female-only rearing showed relative enrichment of genes annotated to stress resistance and nitrogen fixation. These findings provide a genome-resolved foundation for testing how social rearing conditions covary with gut microbiome composition and functional potential in female crickets. Full article